Mixed-mode oscillations in a three time-scale system of ODEs motivated by a neuronal model

We present a mathematical study of some aspects of mixed-mode oscillation (MMO) dynamics in a three time-scale system of ODEs as well as analyse related features of a biophysical model of a neuron from the entorhinal cortex that serves as a motivation for our study. The neuronal model includes standard spiking currents (sodium and potassium) that play a critical role in the analysis of the interspike interval as well as persistent sodium and slow potassium (M) currents. We reduce the dimensionality of the neuronal model from six to three dimensions in order to investigate a regime in which MMOs are generated and to motivate the three time-scale model system upon which we focus our study. We further analyse in detail the mechanism of the transition from MMOs to spiking in our model system. In particular, we prove the existence of a special solution, a singular primary canard, that serves as a transition between MMOs and spiking in the singular limit by employing appropriate rescalings and centre manifold reductions. Additionally, we conjecture that the singular canard solution is the limit of a family of canards and provides numerical evidence for the conjecture.

[1]  M. Hasselmo,et al.  Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons. , 2000, Journal of neurophysiology.

[2]  John Guckenheimer,et al.  Bifurcation, Bursting, and Spike Frequency Adaptation , 1997, Journal of Computational Neuroscience.

[3]  Peter Szmolyan,et al.  Extending Geometric Singular Perturbation Theory to Nonhyperbolic Points - Fold and Canard Points in Two Dimensions , 2001, SIAM J. Math. Anal..

[4]  A. Alonso,et al.  Ionic mechanisms for the subthreshold oscillations and differential electroresponsiveness of medial entorhinal cortex layer II neurons. , 1993, Journal of neurophysiology.

[5]  Christopher Jones,et al.  Geometric singular perturbation theory , 1995 .

[6]  Bard Ermentrout,et al.  Simulating, analyzing, and animating dynamical systems - a guide to XPPAUT for researchers and students , 2002, Software, environments, tools.

[7]  N. Kopell,et al.  Mixed-mode oscillations in a three time-scale model for the dopaminergic neuron. , 2008, Chaos.

[8]  Neil Fenichel Geometric singular perturbation theory for ordinary differential equations , 1979 .

[9]  Horacio G. Rotstein,et al.  Canard Induced Mixed-Mode Oscillations in a Medial Entorhinal Cortex Layer II Stellate Cell Model , 2008, SIAM J. Appl. Dyn. Syst..

[10]  T. Dugladze,et al.  Subthreshold membrane potential oscillations in neurons of deep layers of the entorhinal cortex , 1998, Neuroscience.

[11]  Neil Fenichel Persistence and Smoothness of Invariant Manifolds for Flows , 1971 .

[12]  Incomplete approach to homoclinicity in a model with bent-slow manifold geometry , 2000, nlin/0001030.

[13]  M. Koper Bifurcations of mixed-mode oscillations in a three-variable autonomous Van der Pol-Duffing model with a cross-shaped phase diagram , 1995 .

[14]  Martin Wechselberger,et al.  Existence and Bifurcation of Canards in ℝ3 in the Case of a Folded Node , 2005, SIAM J. Appl. Dyn. Syst..

[15]  N. Brunel,et al.  From subthreshold to firing-rate resonance. , 2003, Journal of neurophysiology.

[16]  Helwig Löffelmann,et al.  GEOMETRY OF MIXED-MODE OSCILLATIONS IN THE 3-D AUTOCATALATOR , 1998 .

[17]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[18]  Jianzhong Su,et al.  Analysis of a Canard Mechanism by Which Excitatory Synaptic Coupling Can Synchronize Neurons at Low Firing Frequencies , 2004, SIAM J. Appl. Math..

[19]  A. Alonso,et al.  Oscillatory Activity in Entorhinal Neurons and Circuits: Mechanisms and Function , 2000, Annals of the New York Academy of Sciences.

[20]  Pierre Gaspard,et al.  The modeling of mixed‐mode and chaotic oscillations in electrochemical systems , 1992 .

[21]  J. Rubin,et al.  The selection of mixed-mode oscillations in a Hodgkin-Huxley model with multiple timescales. , 2008, Chaos.

[22]  A. Alonso,et al.  Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons , 2001, Neuroscience.

[23]  Freddy Dumortier,et al.  Canard Cycles and Center Manifolds , 1996 .

[24]  John Guckenheimer,et al.  Asymptotic analysis of subcritical Hopf-homoclinic bifurcation , 2000 .

[25]  J. B. Ranck,et al.  Generation of theta rhythm in medial entorhinal cortex of freely moving rats , 1980, Brain Research.

[26]  John Guckenheimer,et al.  Singular Hopf Bifurcation in Systems with Two Slow Variables , 2008, SIAM J. Appl. Dyn. Syst..

[27]  Teresa Ree Chay,et al.  BURSTING, SPIKING, CHAOS, FRACTALS, AND UNIVERSALITY IN BIOLOGICAL RHYTHMS , 1995 .

[28]  G. Buzsáki Two-stage model of memory trace formation: A role for “noisy” brain states , 1989, Neuroscience.

[29]  R. Larter,et al.  Chaos via mixed-mode oscillations , 1991, Philosophical Transactions of the Royal Society of London. Series A: Physical and Engineering Sciences.

[30]  Françoise Argoul,et al.  Homoclinic chaos in chemical systems , 1993 .

[31]  Kenneth Showalter,et al.  Nonlinear Chemical Dynamics: Oscillations, Patterns, and Chaos , 1996 .

[32]  A. M. Zhabotinskii [PERIODIC COURSE OF THE OXIDATION OF MALONIC ACID IN A SOLUTION (STUDIES ON THE KINETICS OF BEOLUSOV'S REACTION)]. , 1964, Biofizika.

[33]  J. Carr Applications of Centre Manifold Theory , 1981 .

[34]  Wiktor Eckhaus,et al.  Relaxation oscillations including a standard chase on French ducks , 1983 .

[35]  Nancy Kopell,et al.  Synchronization of Strongly Coupled Excitatory Neurons: Relating Network Behavior to Biophysics , 2003, Journal of Computational Neuroscience.

[36]  Horacio G. Rotstein,et al.  Localized and asynchronous patterns via canards in coupled calcium oscillators , 2006 .

[37]  Robert Clewley,et al.  A Computational Tool for the Reduction of Nonlinear ODE Systems Possessing Multiple Scales , 2005, Multiscale Model. Simul..

[38]  J. Winson Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. , 1978, Science.

[39]  A. Alonso,et al.  Cell-type specific modulation of intrinsic firing properties and subthreshold membrane oscillations by the M(Kv7)-current in neurons of the entorhinal cortex. , 2007, Journal of neurophysiology.

[40]  G. Buzsáki,et al.  Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  Horacio G. Rotstein,et al.  The dynamic structure underlying subthreshold oscillatory activity and the onset of spikes in a model of medial entorhinal cortex stellate cells , 2006, Journal of Computational Neuroscience.

[42]  R. S. Jones,et al.  Synchronous discharges in the rat entorhinal cortex in vitro: Site of initiation and the role of excitatory amino acid receptors , 1990, Neuroscience.

[43]  P. Szmolyan,et al.  Canards in R3 , 2001 .

[44]  Martin Krupa,et al.  Mixed Mode Oscillations due to the Generalized Canard Phenomenon , 2006 .

[45]  J. Callot,et al.  Chasse au canard , 1977 .

[46]  Marc J. Diener Regularizing microscopes and rivers , 1994 .

[47]  É. Benoît,et al.  Canards et enlacements , 1990 .

[48]  M. Hasselmo,et al.  Graded persistent activity in entorhinal cortex neurons , 2002, Nature.

[49]  Georgi S. Medvedev,et al.  Multimodal regimes in a compartmental model of the dopamine neuron , 2004 .

[50]  Georgi Medvedev,et al.  Multimodal oscillations in systems with strong contraction , 2007 .

[51]  A. Alonso,et al.  Neuronal sources of theta rhythm in the entorhinal cortex of the rat , 1987, Experimental Brain Research.

[52]  Nancy Kopell,et al.  Mixed-Mode Oscillations in Three Time-Scale Systems: A Prototypical Example , 2008, SIAM J. Appl. Dyn. Syst..

[53]  Eugene M. Izhikevich,et al.  Dynamical Systems in Neuroscience: The Geometry of Excitability and Bursting , 2006 .

[54]  É. Benoît Chasse au canard , 1980 .

[55]  M. Hasselmo,et al.  Mechanism of Graded Persistent Cellular Activity of Entorhinal Cortex Layer V Neurons , 2006, Neuron.

[56]  A. Alonso,et al.  Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II. , 1993, Journal of neurophysiology.